University of Health Science

Rhinosinusitis is a significant and increasing health problem which results in a large financial burden on society. This evidence based position paper describes what is known about rhinosinusitis and nasal polyps, offers evidence based recommendations on diagnosis and treatment, and considers how we can make progress with research in this area. Rhinitis and sinusitis usually coexist and are concurrent in most individuals; thus, the correct terminology is now rhinosinusitis. Rhinosinusitis (including nasal polyps) is defined as inflammation of the nose and the paranasal sinuses characterised by two or more symptoms, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), +/- facial pain/pressure, +/- reduction or loss of smell; and either endoscopic signs of polyps and/or mucopurulent discharge primarily from middle meatus and/or; oedema/mucosal obstruction primarily in middle meatus, and/or CT changes showing mucosal changes within the ostiomeatal complex and/or sinuses. The paper gives different definitions for epidemiology, first line and second line treatment and for research. Furthermore the paper describes the anatomy and (patho)physiology, epidemiology and predisposing factors, inflammatory mechanisms, evidence based diagnosis, medical and surgical treatment in acute and chronic rhinosinusitis and nasal polyposis in adults and children. Evidence based schemes for diagnosis and treatment are given for the first and second line clinicians. Moreover attention is given to complications and socio-economic cost of chronic rhinosinusitis and nasal polyps. Last but not least the relation to the lower airways is discussed.

BACKGROUND: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. METHODS: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. FINDINGS: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population. INTERPRETATION: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group. FUNDING: The Bill & Melinda Gates Foundation.

Contributing Authors Isam Alobid, MD, PhD 1 , Nithin D. Adappa, MD 2 , Henry P. Barham, MD 3 , Thiago Bezerra, MD 4 , Nadieska Caballero, MD 5 , Eugene G. Chang, MD 6 , Gaurav Chawdhary, MD 7 , Philip Chen, MD 8 , John P. Dahl, MD, PhD 9 , Anthony Del Signore, MD 10 , Carrie Flanagan, MD 11 , Daniel N. Frank, PhD 12 , Kai Fruth, MD, PhD 13 , Anne Getz, MD 14 , Samuel Greig, MD 15 , Elisa A. Illing, MD 16 , David W. Jang, MD 17 , Yong Gi Jung, MD 18 , Sammy Khalili, MD, MSc 19 , Cristobal Langdon, MD 20 , Kent Lam, MD 21 , Stella Lee, MD 22 , Seth Lieberman, MD 23 , Patricia Loftus, MD 24 , Luis Macias‐Valle, MD 25 , R. Peter Manes, MD 26 , Jill Mazza, MD 27 , Leandra Mfuna, MD 28 , David Morrissey, MD 29 , Sue Jean Mun, MD 30 , Jonathan B. Overdevest, MD, PhD 31 , Jayant M. Pinto, MD 32 , Jain Ravi, MD 33 , Douglas Reh, MD 34 , Peta L. Sacks, MD 35 , Michael H. Saste, MD 36 , John Schneider, MD, MA 37 , Ahmad R. Sedaghat, MD, PhD 38 , Zachary M. Soler, MD 39 , Neville Teo, MD 40 , Kota Wada, MD 41 , Kevin Welch, MD 42 , Troy D. Woodard, MD 43 , Alan Workman 44 , Yi Chen Zhao, MD 45 , David Zopf, MD 46 Contributing Author Affiliations 1 Universidad de Barcelona; 2 University of Pennsylvania; 3 Louisiana State University Health Sciences Center; 4 Universidade de São Paulo; 5 ENT Specialists of Illinois; 6 University of Arizona; 7 University of Oxford; 8 University of Texas; 9 University of Indiana; 10 Mount Sinai Beth Israel; 11 Emory University; 12 University of Colorado; 13 Wiesbaden, Germany; 14 University of Colorado; 15 University of Alberta; 16 University of Alabama at Birmingham; 17 Duke University; 18 Sungkyunkwan University; 19 University of Pennsylvania; 20 Universidad de Barcelona; 21 Northwestern University; 22 University of Pittsburgh; 23 New York University; 24 Emory University; 25 University of British Columbia; 26 Yale University School of Medicine; 27 Private Practice; 28 Department of Otolaryngology, Hôtel‐Dieu Hospital, Centre de Recherche du Centre Hospitalier de l'Université de Montréal; 29 University of Adelaide; 30 Pusan National University; 31 University of California, San Francisco; 32 University of Chicago; 33 University of Auckland; 34 Johns Hopkins University; 35 University of New South Wales, Australia; 36 Stanford University; 37 Washington University; 38 Harvard Medical School; 39 Medical University of South Carolina; 40 Singapore General Hospital; 41 Taho University; 42 Northwestern University; 43 Cleveland Clinic Foundation; 44 University of Pennsylvania; 45 University of Adelaide; 46 University of Michigan

Conventionally, “elderly” has been defined as a chronological age of 65 years old or older, while those from 65 through 74 years old are referred to as “early elderly” and those over 75 years old as “late elderly.” However, the evidence on which this definition is based is unknown. We have attempted to review the definition of elderly by analyzing data from long‐term longitudinal epidemiological studies, and clinical and pathological studies that have been accumulated at the Tokyo Metropolitan Geriatric Hospital and the Tokyo Metropolitan Institute of Gerontology. Our recommendation might be a starting point in developing a strategy for a successful society by reviewing the definition of elderly based on comprehensive evidence in all aspects of social, cultural and medical sciences.

BACKGROUND: The emergence of artemisinin-resistant Plasmodium falciparum in Southeast Asia threatens malaria treatment efficacy. Mutations in a kelch protein encoded on P. falciparum chromosome 13 (K13) have been associated with resistance in vitro and in field samples from Cambodia. METHODS: P. falciparum infections from artesunate efficacy trials in Bangladesh, Cambodia, Laos, Myanmar, and Vietnam were genotyped at 33 716 genome-wide single-nucleotide polymorphisms (SNPs). Linear mixed models were used to test associations between parasite genotypes and parasite clearance half-lives following artesunate treatment. K13 mutations were tested for association with artemisinin resistance, and extended haplotypes on chromosome 13 were examined to determine whether mutations arose focally and spread or whether they emerged independently. RESULTS: The presence of nonreference K13 alleles was associated with prolonged parasite clearance half-life (P = 1.97 × 10(-12)). Parasites with a mutation in any of the K13 kelch domains displayed longer parasite clearance half-lives than parasites with wild-type alleles. Haplotype analysis revealed both population-specific emergence of mutations and independent emergence of the same mutation in different geographic areas. CONCLUSIONS: K13 appears to be a major determinant of artemisinin resistance throughout Southeast Asia. While we found some evidence of spreading resistance, there was no evidence of resistance moving westward from Cambodia into Myanmar.

OBJECTIVE: To identify the most accurate cognitive measures in discriminating between individuals with presymptomatic AD and individuals who remained nondemented. METHODS: During a 10-year prospective community study, 120 nondemented subjects completed a battery of standard cognitive tests and clinically manifested AD 1.5 years later. Performance on each of 16 cognitive tests was compared between these 120 presymptomatic cases and 483 controls who remained nondemented over the 10-year follow-up period. The area under the receiver operating characteristic (AUC) curve for each test was used to measure its accuracy of discrimination between cases and controls. RESULTS: Among the 16 neuropsychological tests, Word List Delayed Recall discriminated best between cases and controls (AUC = 0.806), followed by the Word List 3rd Learning Trial (0.787), Word List 1st Learning Trial (0.774), and Trail-making Test B (0.773), compared to the Mini-Mental State Examination (MMSE) (0.726). Both Word List Delayed Recall and Word List 3rd Learning Trial were significantly more accurate than the MMSE. The combination of Word List Delayed Recall and Trail-making Test B comprised the optimal set of cognitive measures, with the highest AUC (0.852). CONCLUSION: Measures of delayed recall and executive functions were the best discriminators between those who would manifest AD 1.5 years later and those who would remain nondemented. These findings are relevant for the early detection of AD and, therefore, for prevention and early intervention trials. Executive dysfunction may be a subtle manifestation of incipient AD, along with memory dysfunction.

This study examines the interconnections among education--as a proxy for socioeconomic status--stress, and physical and mental healthy by specifying differential exposure and vulnerability models using data from The National Study of Daily Experiences (N = 1,031). These daily diary data allowed assessment of the social distribution of a qualitatively different type of stressor than has previously been examined in sociological stress research--daily stressors, or hassles. Moreover, these data allowed a less biased assessment of stress exposure and a more micro-level examination of the connections between stress and healthy by socioeconomic status. Consistent with the broad literature describing socioeconomic inequalities in physical and mental health, the results of this study indicated that, on any given day, better-educated adults reported fewer physical symptoms and less psychological distress. Although better educated individuals reported more daily stressors, stressors reported by those with less education were more severe. Finally, neither exposure nor vulnerability explained socioeconomic differentials in daily health, but the results clearly indicate that the stressor-health association cannot be considered independent of socioeconomic status.

Although men and women show similar rates of obesity, women more frequently engage in weight loss efforts, with potentially adverse health consequences. We surveyed 320 college-aged men and women to examine gender differences in the determinants of body dissatisfaction and the degree of importance assigned to bodyweight and shape. Results indicated that, for both genders, satisfaction with bodyweight and shape decreased as body mass index (BMI) increased. Women, however, showed significantly greater body and weight dissatisfaction than men at most weight categories. Only the underweight (BMI < 20) women and men were similarly satisfied with their bodyweight and shape. As BMI increased, however, women became disproportionately more dissatisfied: both normal-weight and overweight women expressed greater dissatisfaction than comparable men. College-aged women also attributed progressively more importance to both weight and shape as BMI increased, unlike college-aged men, who considered body weight equally important to (or slightly less important than) self-esteem as BMI increased. We discuss implications for the self-esteem of obese women and men.

It seems that coronaviruses take an important place in the 21th century history. Five of seven human coronavirus was isolated in this century. Unfortunately, last three of them entered our life with a fear of outbreak, pandemic or death. Last human coronavirus which emerged world from Wuhan China, SARS CoV-2 and its clinical expression, Coronavirus disease (COVID-19) recently taken a significant place in our daily practice. Initial reports showed that, its origin was bats. It transmitted human to human by droplet and contact routes, but some doubt about airborne, fecal or intrauterine transmission also should be removed. Its R0 value is 2.3 but it could be as high as 5.7. Its case fatality rate was 6.3, but it was different in different ages and counties, and it could be over 15%. According to early models total 10–12 weeks is required to control an outbreak in the community. While different countries show different daily case numbers, total number of case, case mortality rates or R0, it seems they show a similar epidemic curve. Every day we learn new data about the current outbreak. Since the outbreak is not over yet, every detail should be evaluated carefully and the updates should be followed closely to monitor the epidemiological properties of COVID-19.

BACKGROUND: Cryptococcal meningitis associated with human immunodeficiency virus (HIV) infection causes more than 600,000 deaths each year worldwide. Treatment has changed little in 20 years, and there are no imminent new anticryptococcal agents. The use of adjuvant glucocorticoids reduces mortality among patients with other forms of meningitis in some populations, but their use is untested in patients with cryptococcal meningitis. METHODS: In this double-blind, randomized, placebo-controlled trial, we recruited adult patients with HIV-associated cryptococcal meningitis in Vietnam, Thailand, Indonesia, Laos, Uganda, and Malawi. All the patients received either dexamethasone or placebo for 6 weeks, along with combination antifungal therapy with amphotericin B and fluconazole. RESULTS: The trial was stopped for safety reasons after the enrollment of 451 patients. Mortality was 47% in the dexamethasone group and 41% in the placebo group by 10 weeks (hazard ratio in the dexamethasone group, 1.11; 95% confidence interval [CI], 0.84 to 1.47; P=0.45) and 57% and 49%, respectively, by 6 months (hazard ratio, 1.18; 95% CI, 0.91 to 1.53; P=0.20). The percentage of patients with disability at 10 weeks was higher in the dexamethasone group than in the placebo group, with 13% versus 25% having a prespecified good outcome (odds ratio, 0.42; 95% CI, 0.25 to 0.69; P<0.001). Clinical adverse events were more common in the dexamethasone group than in the placebo group (667 vs. 494 events, P=0.01), with more patients in the dexamethasone group having grade 3 or 4 infection (48 vs. 25 patients, P=0.003), renal events (22 vs. 7, P=0.004), and cardiac events (8 vs. 0, P=0.004). Fungal clearance in cerebrospinal fluid was slower in the dexamethasone group. Results were consistent across Asian and African sites. CONCLUSIONS: Dexamethasone did not reduce mortality among patients with HIV-associated cryptococcal meningitis and was associated with more adverse events and disability than was placebo. (Funded by the United Kingdom Department for International Development and others through the Joint Global Health Trials program; Current Controlled Trials number, ISRCTN59144167.).

Background: Poor health-related quality of life (HRQL) is common in heart failure (HF), but there are few data on HRQL in HF and the association between HRQL and mortality outside Western countries. Methods: We used the Kansas City Cardiomyopathy Questionnaire–12 (KCCQ-12) to record HRQL in 23 291 patients with HF from 40 countries in 8 different world regions in the G-CHF study (Global Congestive Heart Failure). We compared standardized KCCQ-12 summary scores (adjusted for age, sex, and markers of HF severity) among regions (scores range from 0 to 100, with higher score indicating better HRQL). We used multivariable Cox regression with adjustment for 15 variables to assess the association between KCCQ-12 summary scores and the composite of all-cause death, HF hospitalization, and each component over a median follow-up of 1.6 years. Results: The mean age of participants was 65 years; 61% were men; 40% had New York Heart Association class III or IV symptoms; and 46% had left ventricular ejection fraction ≥40%. Average HRQL differed between regions (lowest in Africa [mean± SE, 39.5±0.3], highest in Western Europe [62.5±0.4]). There were 4460 (19%) deaths, 3885 (17%) HF hospitalizations, and 6949 (30%) instances of either event. Lower KCCQ-12 summary score was associated with higher risk of all outcomes; the adjusted hazard ratio (HR) for each 10-unit KCCQ-12 summary score decrement was 1.18 (95% CI, 1.17–1.20) for death. Although this association was observed in all regions, it was less marked in South Asia, South America, and Africa (weakest association in South Asia: HR, 1.08 [95% CI, 1.03–1.14]; strongest association in Eastern Europe: HR, 1.31 [95% CI, 1.21–1.42]; interaction P &lt;0.0001). Lower HRQL predicted death in patients with New York Heart Association class I or II and III or IV symptoms (HR, 1.17 [95% CI, 1.14–1.19] and HR, 1.14 [95% CI, 1.12–1.17]; interaction P =0.13) and was a stronger predictor for the composite outcome in New York Heart Association class I or II versus class III or IV (HR 1.15 [95% CI, 1.13–1.17] versus 1.09 [95% CI, [1.07–1.11]; interaction P &lt;0.0001). HR for death was greater in ejection fraction ≥40 versus &lt;40% (HR, 1.23 [95% CI, 1.20–1.26] and HR, 1.15 [95% CI, 1.13–1.17]; interaction P &lt;0.0001). Conclusion: HRQL is a strong and independent predictor of all-cause death and HF hospitalization across all geographic regions, in mildly and severe symptomatic HF, and among patients with preserved and reduced ejection fraction. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03078166.

The recent emergence of artemisinin-resistant Plasmodium falciparum malaria in western Cambodia could threaten prospects for malaria elimination. Identification of the genetic basis of resistance would provide tools for molecular surveillance, aiding efforts to contain resistance. Clinical trials of artesunate efficacy were conducted in Bangladesh, in northwestern Thailand near the Myanmar border, and at two sites in western Cambodia. Parasites collected from trial participants were genotyped at 8,079 single nucleotide polymorphisms (SNPs) using a P. falciparum-specific SNP array. Parasite genotypes were examined for signatures of recent positive selection and association with parasite clearance phenotypes to identify regions of the genome associated with artemisinin resistance. Four SNPs on chromosomes 10 (one), 13 (two), and 14 (one) were significantly associated with delayed parasite clearance. The two SNPs on chromosome 13 are in a region of the genome that appears to be under strong recent positive selection in Cambodia. The SNPs on chromosomes 10 and 13 lie in or near genes involved in postreplication repair, a DNA damage-tolerance pathway. Replication and validation studies are needed to refine the location of loci responsible for artemisinin resistance and to understand the mechanism behind it; however, two SNPs on chromosomes 10 and 13 may be useful markers of delayed parasite clearance in surveillance for artemisinin resistance in Southeast Asia.

We tested the effects of 3 mood inductions (neutral, positive, and negative) on food intake in 91 women of varying degrees of dietary restraint. Mood induction was accomplished by exposure to 1 of 3 film segments: a travelogue (neutral affect), a comedy film (positive affect), and a horror film (negative affect). In subjects exposed to the neutral film, food intake decreased with increasing levels of dietary restraint. Among subjects who viewed either the comedy film or the horror film, however, food intake increased with increasing restraint. Although the horror film appeared to be more disinhibiting than the comedy film, this effect may have resulted from a difference in the intensity of the emotions induced rather than from their valence. These results suggest that emotional arousal, regardless of valence, may trigger overeating among restrained eaters.

Background Cryptococcal meningitis is a leading cause of human immunodeficiency virus (HIV)–related death in sub-Saharan Africa. Whether a treatment regimen that includes a single high dose of liposomal amphotericin B would be efficacious is not known. Methods In this phase 3 randomized, controlled, noninferiority trial conducted in five African countries, we assigned HIV-positive adults with cryptococcal meningitis in a 1:1 ratio to receive either a single high dose of liposomal amphotericin B (10 mg per kilogram of body weight) on day 1 plus 14 days of flucytosine (100 mg per kilogram per day) and fluconazole (1200 mg per day) or the current World Health Organization–recommended treatment, which includes amphotericin B deoxycholate (1 mg per kilogram per day) plus flucytosine (100 mg per kilogram per day) for 7 days, followed by fluconazole (1200 mg per day) for 7 days (control). The primary end point was death from any cause at 10 weeks; the trial was powered to show noninferiority at a 10-percentage-point margin. Results A total of 844 participants underwent randomization; 814 were included in the intention-to-treat population. At 10 weeks, deaths were reported in 101 participants (24.8%; 95% confidence interval [CI], 20.7 to 29.3) in the liposomal amphotericin B group and 117 (28.7%; 95% CI, 24.4 to 33.4) in the control group (difference, −3.9 percentage points); the upper boundary of the one-sided 95% confidence interval was 1.2 percentage points (within the noninferiority margin; P<0.001 for noninferiority). Fungal clearance from cerebrospinal fluid was −0.40 log10 colony-forming units (CFU) per milliliter per day in the liposomal amphotericin B group and −0.42 log10 CFU per milliliter per day in the control group. Fewer participants had grade 3 or 4 adverse events in the liposomal amphotericin B group than in the control group (50.0% vs. 62.3%). Conclusions Single-dose liposomal amphotericin B combined with flucytosine and fluconazole was noninferior to the WHO-recommended treatment for HIV-associated cryptococcal meningitis and was associated with fewer adverse events.

Glutamine and glutamate transport activities were measured in isolated luminal and abluminal plasma membrane vesicles derived from bovine brain endothelial cells. Facilitative systems for glutamine and glutamate were almost exclusively located in luminal-enriched membranes. The facilitative glutamine carrier was neither sensitive to 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid inhibition nor did it participate in accelerated amino acid exchange; it therefore appeared to be distinct from the neutral amino acid transport system L1. Two Na-dependent glutamine transporters were found in abluminal-enriched membranes: systems A and N. System N accounted for approximately 80% of Na-dependent glutamine transport at 100 microM. Abluminal-enriched membranes showed Na-dependent glutamate transport activity. The presence of 1) Na-dependent carriers capable of pumping glutamine and glutamate from brain into endothelial cells, 2) glutaminase within endothelial cells to hydrolyze glutamine to glutamate and ammonia, and 3) facilitative carriers for glutamine and glutamate at the luminal membrane may provide a mechanism for removing nitrogen and nitrogen-rich amino acids from brain.

It has been suggested that the normal aging process is characterized by a pattern of neuropsychological performance decline that implies relatively greater vulnerability of right-hemisphere functions. This hypothesis was tested in a sample of 68 volunteers aged 20-75 who were free of systemic and neurologic illness. Neuropsychologic measures of lateralized and focal function were specifically selected to eliminate systematic procedural differences among tests (e.g., timed vs. untimed, overlearned vs. unfamiliar). Inferences about the localizing significance of each measure were based on previously demonstrated double dissociation of function in lesion studies. Results suggested that declines in cerebral efficiency are not differentially lateralized. Age correlated performance changes implied bilateral reduction that was significantly more pronounced on operations associated with frontal-lobe function. Anatomic and theoretical explanations for this pattern were discussed.

Primary adrenal insufficiency is life threatening and can present alone or in combination with other comorbidities. Here, we have described a primary adrenal insufficiency syndrome and steroid-resistant nephrotic syndrome caused by loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1). SGPL1 executes the final decisive step of the sphingolipid breakdown pathway, mediating the irreversible cleavage of the lipid-signaling molecule sphingosine-1-phosphate (S1P). Mutations in other upstream components of the pathway lead to harmful accumulation of lysosomal sphingolipid species, which are associated with a series of conditions known as the sphingolipidoses. In this work, we have identified 4 different homozygous mutations, c.665G>A (p.R222Q), c.1633_1635delTTC (p.F545del), c.261+1G>A (p.S65Rfs*6), and c.7dupA (p.S3Kfs*11), in 5 families with the condition. In total, 8 patients were investigated, some of whom also manifested other features, including ichthyosis, primary hypothyroidism, neurological symptoms, and cryptorchidism. Sgpl1-/- mice recapitulated the main characteristics of the human disease with abnormal adrenal and renal morphology. Sgpl1-/- mice displayed disrupted adrenocortical zonation and defective expression of steroidogenic enzymes as well as renal histology in keeping with a glomerular phenotype. In summary, we have identified SGPL1 mutations in humans that perhaps represent a distinct multisystemic disorder of sphingolipid metabolism.

Background: Pneumonia, the leading infectious cause of child mortality globally, mainly afflicts developing countries. This prospective observational study aimed to assess the microorganisms associated with pneumonia in children aged <5 years in developing and emerging countries. Methods: A multicenter, case-control study by the GABRIEL (Global Approach to Biological Research, Infectious diseases and Epidemics in Low-income countries) network was conducted between 2010 and 2014 in Cambodia, China, Haiti, India (2 sites), Madagascar, Mali, Mongolia, and Paraguay. Cases were hospitalized children with radiologically confirmed pneumonia; controls were children from the same setting without any features suggestive of pneumonia. Nasopharyngeal swabs were collected from all subjects; 19 viruses and 5 bacteria were identified by reverse-transcription polymerase chain reaction. Associations between microorganisms and pneumonia were quantified by calculating the adjusted population attributable fraction (aPAF) after multivariate logistic regression analysis adjusted for sex, age, time period, other pathogens, and site. Results: Overall, 888 cases and 870 controls were analyzed; ≥1 microorganism was detected in respiratory samples in 93.0% of cases and 74.4% of controls (P < .001). Streptococcus pneumoniae, Mycoplasma pneumoniae, human metapneumovirus, rhinovirus, respiratory syncytial virus (RSV), parainfluenza virus 1, 3, and 4, and influenza virus A and B were independently associated with pneumonia; aPAF was 42.2% (95% confidence interval [CI], 35.5%-48.2%) for S. pneumoniae, 18.2% (95% CI, 17.4%-19.0%) for RSV, and 11.2% (95% CI, 7.5%-14.7%) for rhinovirus. Conclusions: Streptococcus pneumoniae, RSV, and rhinovirus may be the major microorganisms associated with pneumonia infections in children <5 years of age from developing and emerging countries. Increasing S. pneumoniae vaccination coverage may substantially reduce the burden of pneumonia among children in developing countries.

We tested the effects of film-induced negative affect (i.e., exposure to a frightening film) in 60 women classified as either restrained or unrestrained eaters on the basis of their responses to the Revised Restraint Scale (Herman & Polivy, 1980). Exposure to the frightening film, in contrast to a neutral film, was associated with increases in anxiety, sadness, and anger. High restraint subjects exposed to the frightening film ate more than did equally restrained subjects exposed to a neutral film or low restraint subjects exposed to either film. Thus, negative affect triggered overeating among restrained eaters. Although unrestrained eaters exposed to the frightening film ate less than those who viewed the neutral film, this difference was not statistically significant. These results suggest that negative affect may prompt overeating in persons who attempt to restrict their caloric intake.

Influenza-associated encephalopathy, a severe neurologic complication of influenza, is being reported more frequently in Japan. We investigated the transcription of cytokine genes in peripheral blood leukocytes and compared patients with influenza and with encephalopathy or febrile convulsions and patients with influenza but without neurologic complications. A quantitative polymerase chain reaction (PCR) revealed that transcription of the interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha genes was up-regulated to a greater extent in patients with encephalopathy than in those without neurologic complications. Plasma IL-6 levels also were higher in patients with encephalopathy, although the difference was marginal. Viral RNA in throat swabs was quantified using a real-time quantitative PCR. The virus load was similar among patients with encephalopathy or febrile convulsions or without neurologic complications. Furthermore, virus load was not correlated with either the transcription of cytokine genes or plasma cytokine concentrations. These results suggest that influenza-associated encephalopathy might be a consequence of systemic immune responses.